9982. Vinblastine
Nomenclature
Description and references
Antitumor alkaloid isolated from periwinkle, Vinca rosea Linn., Apocynaceae; inhibits microtubule assembly. Identification: R. L. Noble et al., Ann. N.Y. Acad. Sci. 76, 882-894 (1958). Isolation and characterization: M. Gorman et al., J. Am. Chem. Soc. 81, 4745, 4754 (1959); C. T. Beer et al., US 3097137 (1963 to CPD Ltd.). Structure: N. Neuss et al., J. Am. Chem. Soc. 86, 1440 (1964). 13C-NMR spectral analysis: E. Wenkert et al., Helv. Chim. Acta 58, 1560 (1975). Synthesis from catharanthine and vindoline, q.q.v.: P. Mangeney et al., J. Am. Chem. Soc. 101, 2243 (1979); J. P. Kutney et al., Heterocycles 27, 1845 (1988). Enantioselective synthesis: M. E. Kuehne et al., J. Org. Chem. 56, 513 (1991). Toxicology: C. Lu, M. Meistrich, Cancer Res. 39, 3575 (1979). Clinical trial in combination with bleomycin, methotrexate in Hodgkin's disease: P. G. Gobbi et al., J. Clin. Oncol. 14, 527 (1996). Review of pharmacology, toxicology and pharmacokinetics: W. P. Brade, Beitr. Onkol. 6, 95-123 (1981). Comprehensive description: F. J. Muhtadi, A. F. A. Afify, Anal. Profiles Drug Subs. Excip. 21, 611-658 (1992).
Properties
Solvated needles from methanol, mp 211-216°. [α]D23 32° (c = 0.88 in methanol). uv max (ethanol): 214, 259 nm (log ε 4.74, 4.22). pKa1 5.4; pKa2 7.4. Practically insol in water, petr ether. Sol in alcohols, acetone, ethyl acetate, CHCl3.Derivative
Sulfate.Nomenclature
Properties
Crystallizes as hydrate, mp 284-285°. [α]D26 28° (c = 1.01 in methanol). uv max (methanol): 212, 262, 284, 292 nm (log ε 4.75, 4.28, 4.22, 4.18). Very slightly sol in ethanol. Practically insol in ether. One part is sol in 10 parts of water, 50 parts of chloroform. LD50 i.v. in mice: 9.5 mg/kg (Lu, Meistrich).Therapeutic Category
Antineoplastic.
Therapeutic Category (Veterinary)
Antineoplastic.Keywords
Antineoplastic; Alkaloids/Natural Products; Vinca Alkaloids